Skin cancer has become an epidemic in the US, and most of it arises from solar UV damage to DNA. Applied Genetics has developed a new approach, using DNA repair enzymes delivered by liposomes to prevent UV-induced skin cancer. The first generation of product, T4N5 liposomes, is in Phase III clinical testing. This proposal is to develop the next generation of DNA repair enzymes, using a new photolyase with specificity for the <6-4> photoproduct, and a new endonuclease with specificity for both cyclobutane pyrimidine dimers and <6-4> photoproducts. The Phase I plan is to demonstrate the feasibility of encapsulating these new enzymes in liposomes. This includes the development of new reagents and assays for their activities, and to assay the activity and stability of these enzymes in liposomes. If either of both of these enzymes prove useful, then the plan is to advance to the Phase II testing to establish their effectiveness in cell culture and animal systems. PROPOSED COMMERCIAL APPLICATION: The research will lead directly to the pre-clinical and clinical testing of new products to prevent skin cancer. The data gathered in these studies will be used to evaluate new DNA repair liposomes for activity, stability and safety, and will be used in documents to support an Investigational New Drug application. Approved photoaging and skin cancer prevention products can have sales of $200 million annually.